ASH 2022 | Preliminary results from a first-in-human study of EP0042 in patients with R/R AML
David Taussig, MRCP, FRCPath, PhD, The Royal Marsden NHS Foundation Trust, London, UK, discusses preliminary results from an ongoing Phase I/IIa study which is evaluating the safety and tolerability of EP0042, a dual FLT3 and aurora kinase inhibitor, in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) (NCT04581512). This interview took place at the 64th ASH Annual Meeting and Exposition congress held in New Orleans, LA.
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Transcript (edited for clarity)
I’ve been presenting work from the first-in-human study of a new drug called EP0042. This is a drug which targets a couple of key enzymes. One is called aurora kinase, and that’s involved with cell cycling, so it’s important in proliferating cells. And the second enzyme that we’re targeting with the drug is FLT3, which is a key enzyme in driving acute myeloid leukemia...
I’ve been presenting work from the first-in-human study of a new drug called EP0042. This is a drug which targets a couple of key enzymes. One is called aurora kinase, and that’s involved with cell cycling, so it’s important in proliferating cells. And the second enzyme that we’re targeting with the drug is FLT3, which is a key enzyme in driving acute myeloid leukemia. And we know that previous attempts to improve the outcomes in leukemia have focused on FLT3 alone. But previous researchers have shown that aurora kinase actually can render FLT3 inhibitors ineffective. So by hitting both targets, we hope to make a better anti-leukemia agent, one which is more difficult for the leukemia to evade.
This is a first-in-human study, so we’ve been giving this drug in increasing doses to patients. We’re doing an escalation study and we start down low because we don’t know how the patients are going to cope with it. And you build up the dosing in cohorts of three patients and you look out for dose-limiting toxicity. In the abstract, we didn’t see any at the dose level we presented here, but subsequently we’ve got another cohort where we’ve had some dose-limiting toxicity.
We’ve seen some neurological side effects, some somnolence, sleepiness and some tremor in some patients. But it’s reversible on coming off the drug. And I suspect those patients will just need to dose reduce and put them on a slightly lower dose of the drug. And we’ve seen some responses as well in terms of clearing leukemia cells from the blood of patients, which is exciting. But we’re still trying to get the best dose for the patients. And when you look at the levels of the drug in the patient’s blood, we seem to be getting high enough levels that from the in-vitro data would suggest we are going to effectively hit the aurora kinase and the FLT3 targets. So we’re quite excited about this.
And obviously this is a difficult disease to treat and once we’ve identified the right dose, we’ll do further dose expansion studies and combination studies as well with other drugs that are active in leukemia.
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